The protective effect of metformin (MET) on abdominal aortic aneurysm (AAA) has been reported. However, the related mechanism is still poor understood. In this study, we deeply investigated the role of metformin in AAA pathophysiology. Angiotensin II (Ang-II) was used to construct the AAA model in ApoE−/− mice. The related mechanism was explored using Western blot and quantitative real time PCR (qRT-PCR). We also observed the morphological changes in the abdominal aorta and the influence of metformin on biological behaviors of rat abdominal aortic VSMCs. The PI3K/AKT/mTOR pathway was activated in aneurysmal wall tissues of AAA patients and rat model. Treatment with metformin inhibited the breakage and preserved the elastin structure of the aorta, the loss of collagen, and the apoptosis of aortic cells. In addition, metformin significantly suppressed the activation of the PI3K/AKT/mToR pathway and decreased the mRNA and protein levels of LC3B and Beclin1, which were induced by Ang-II. Moreover, PI3K inhibitors enhanced the effect of metformin while PI3K agonists largely reversed this effect. Interestingly, the cell proliferation, apoptosis, migration and autophagy of vascular smooth muscle cells (VSMCs) induced by Ang-II were also decreased following metformin treatment. PI3K inhibitors and agonists strengthened and weakened the effects of metformin in VSMCs, respectively. Metformin represses the pathophysiology of AAA by inhibiting the activation of PI3K/AKT/mTOR/autophagy pathway. This repression may be useful as a new therapeutic strategy for AAA.

Deep vein thrombosis (DVT) is a rare cause of arteriovenous fistula (AVF). The pathogenesis of acquired AVF after DVT remains unclear, and publications focusing on therapy and follow-up are also inadequate. In this study, the diagnosis and treatment of 24 patients with acquired AVF in the lower extremity after DVT was reported. This is a retrospective study. We studied 24 patients with acquired AVF after DVT who were screened by ultrasound and confirmed by arteriography or computed tomographic arteriography (CTA) in our hospital. Treatments included simple compression therapy (SCT), venous hypertension-relieving therapy (VHRT) and transarterial embolization; VHRT included iliac vein stenting and Palma-Dale surgery (fem-fem bypass). All 24 patients exhibited symptoms in the left lower extremity including swelling (24 cases, 100%), pain (14 cases, 58.33%), pigmentation (13 cases, 54.17%) and ulcers (8 cases, 33.33%). No cardiac enlargement or cardiac insufficiency was reported in any case. The initial ultrasound screening suggested PTS in all 24 cases, with arterialized waveform in veins in 24 cases and high-velocity turbulent flow within the fistulas in 16 cases. The AVF recurrence rate of embolization was 66.7% (4/6). In 7 patients who underwent SCT, the circumference difference of bilateral lower limbs at the 1-year follow-up was not significantly different from that before treatment (thigh, P=0.413; calf, P=0.478). In 14 patients who underwent VHRT, the circumference difference of bilateral lower limbs at the 1-year follow-up was significantly smaller than that before treatment (thigh, P=0.000; calf, P=0.001), and the follow-up difference value of the Venous Insufficiency Epidemiological and Economic Study-Quality of Life (VEINES-QOL) scores was significantly higher than that in the SCT group (1 month, P=0.012; 6 months, P=0.000; 1 year, P=0.000; 2 years, P=0.003). Ultrasound plays an important role in screening and diagnosing AVF. Iliac vein obstruction rather than AVF was most likely the primary cause of the symptoms. Due to the high recurrence rate of DVT, transarterial embolization of AVF is not effective; thus, VHRT should be recommended as the preferred treatment.

Abdominal aortic aneurysm (AAA) is a common and serious disease with a high mortality rate, but its genetic determinants have not been fully identified. In this feasibility study, we aimed to elucidate the transcriptome profile of AAA and further reveal its molecular mechanisms through the Oxford Nanopore Technologies (ONT) MinION platform. Overall, 9574 novel transcripts and 781 genes were identified by comparing and analysing the redundant-removed transcripts of all samples with known reference genome annotations. We characterized the alternative splicing, alternative polyadenylation events and simple sequence repeat (SSR) loci information based on full-length transcriptome data, which would help us further understand the genome annotation and gene structure of AAA. Moreover, we proved that ONT methods were suitable for the identification of lncRNAs via identifying the comprehensive expression profile of lncRNAs in AAA. The results of differentially expressed transcript (DET) analysis showed that a total of 7044 transcripts were differentially expressed, of which 4278 were upregulated and 2766 were downregulated among two groups. In the KEGG analysis, 4071 annotated DETs were involved in human diseases, organismal systems and environmental information processing. These pilot findings might provide novel insights into the pathogenesis of AAA and provide new ideas for the optimization of personalized treatment of AAA, which is worthy of further study in subsequent studies.

Chronic inflammation plays an essential role in the pathogenesis of abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation. Chemerin, a multifunctional adipocytokine, is mainly generated in the liver and adipose tissue. The combination of chemerin and chemokine-like receptor 1 (CMKLR1) has been demonstrated to promote the progression of atherosclerosis, arthritis diseases, and Crohns disease. However, chemerin-9 acts as an analog of chemerin to exert an anti-inflammatory effect by binding to CMKLR1. Here, we first demonstrated that AAA exhibited higher levels of chemerin and CMKLR1 expression compared with the normal aortic tissues. Hence, we hypothesized that the chemerin/CMKLR1 axis might be involved in AAA progression. Moreover, we found that chemerin-9 treatment markedly suppressed inflammatory cell infiltration, neovascularization, and matrix metalloproteinase (MMP) expression, while increasing the elastic fibers and smooth muscle cells (SMCs) in Ang II-induced AAA in ApoE^−/− mice. This demonstrated that chemerin-9 could inhibit AAA formation. Collectively, our findings indicate a potential mechanism underlying AAA progression and suggest that chemerin-9 can be used therapeutically.